Banca de DEFESA: GUILHERME MATOS PASSARINI

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : GUILHERME MATOS PASSARINI
DATA : 02/12/2021
HORA: 14:30
LOCAL: Sala Virtual Remota
TÍTULO:

In vitro, ex vivo and in silico studies of a triterpene against Plasmodium spp

PALAVRAS-CHAVES:

Malaria; Triterpenes; Plasmodium falciparum; Plasmodium vivax; 2-transenoyl-ACP-reductas

PÁGINAS: 93
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biologia Geral
RESUMO:

Malaria is responsible for 200,000 deaths each year on average. Currently, the combination of artemisinin derivatives (ACT) is used as the first-choice treatment against the disease. However, the resistance of ACT-resistant strains motivates alternative sources of compounds with antiplasmodial activity. Thus, the present study aimed to investigate the in vitro, in silico and ex vivo antiplasmodial activity of a trioxidized semi-synthetic triterpene, called CL-1, as well as its cytotoxicity. The study also aimed to analyze the ability of the compound to inhibit the invasion of the merozoites in human red blood cells. Antiplasmodial tests were performed on human erythrocytes infected with the W2 strain of Plasmodium falciparum and evaluated by the Sybr Green fluorimetric technique. Cytotoxicity was performed on HepG2 and VERO cells, and was assessed using MTT assays. Studies of hemolytic action were also carried out, in order to investigate whether the action of the compound on the parasite is direct or indirect; and ex vivo studies performed on patient samples against circulating strains of P. falciparum and P. vivax. Additionally, in silico studies were carried out with the triterpene compound CL-1: molecular docking analysis against the enzyme trans-2-ACP-enoyl-reductase (PfENR) from P. falciparum; and virtual analysis of physicochemical properties. Preliminary results showed that CL-1 has an inhibition value of 50% of the parasite population (IC50) of 19.8 µM against P. falciparum (W2 strain) and a cytotoxic concentration value for 50% of the cell population (CC50) higher than 500 µM for HepG2 and VERO cell lines. Ex vivo experiments demonstrated that CL-1 has IC50 values ranging from 0.1 to 99 µM for the circulating strains of P. falciparum and P. vivax. The compound also showed no hemolytic action against human red blood cells and was not shown to impede the ability to block invasion into the red blood cells. CL-1 also demonstrated in silico interaction with PfENR, with an estimated ∆G of -6.58 kcal/mol, in addition to complying with most of the physicochemical parameters established by Lipinski and Veber. So far, the results indicate that the compound CL-1 has great potential in antimalarial drug development.

MEMBROS DA BANCA:
Presidente - 218.429.088-20 - CAROLINA BIONI GARCIA TELES - FIOCRUZ
Externo à Instituição - ERNESTO RAÚL CAFFARENA - FIOCRUZ
Externo à Instituição - GEISA PAULINO CAPRINI EVARISTO - FIOCRUZ
Externo à Instituição - LEANDRO SOARES MOREIRA - UNIR
Externo à Instituição - LUIZ ANDRE MORAIS MARIÚBA - FIOCRUZ